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Summary: The human intestinal mucosa is a critical site for absorption, distribution, metabolism, and excretion (ADME)/Tox studies in drug development and is difficult to recapitulate in vitro. Using bioprinting, we generated three-dimensional (3D) intestinal tissue composed of human primary intestinal epithelial cells and myofibroblasts with architecture and function to model the native intestine. The 3D intestinal tissue demonstrates a polarized epithelium with tight junctions and specialized epithelial cell types and expresses functional and inducible CYP450 enzymes. The 3D intestinal tissues develop physiological barrier function, distinguish between high- and low-permeability compounds, and have functional P-gp and BCRP transporters. Biochemical and histological characterization demonstrate that 3D intestinal tissues can generate an injury response to compound-induced toxicity and inflammation. This model is compatible with existing preclinical assays and may be implemented as an additional bridge to clinical trials by enhancing safety and efficacy prediction in drug development. : In Vitro Toxicology Including 3D Culture; Bioengineering; Tissue Engineering Subject Areas: In Vitro Toxicology Including 3D Culture, Bioengineering, Tissue Engineering

In the same way that it has transformed the production of other solid objects, additive manufacturing has the power to transform drug discovery and regenerative medicine by enabling the creation of complex and multilayered tissues through an automated platform. The growing number of new bioprinted skin models has the potential to better recapitulate native tissue biology with a degree of complexity, flexibility, and reproducibility not achievable by traditional manual fabrication approaches. In this review, we provide an overview of the current bioprinting approaches being used today, and how they are being applied to fabricate the next generation of ex vivo human skin equivalents for use in toxicology, pharmacological screening, disease modeling, and therapeutic applications.